IE65711B1 - N,N'-di- or N,N'N'-tri-substituted-5- bisaminomethylene-1, 3-dioxane-4,6- dione inhibitors of acyl-CoA: cholesterol-acyl transferase - Google Patents
N,N'-di- or N,N'N'-tri-substituted-5- bisaminomethylene-1, 3-dioxane-4,6- dione inhibitors of acyl-CoA: cholesterol-acyl transferaseInfo
- Publication number
- IE65711B1 IE65711B1 IE290091A IE290091A IE65711B1 IE 65711 B1 IE65711 B1 IE 65711B1 IE 290091 A IE290091 A IE 290091A IE 290091 A IE290091 A IE 290091A IE 65711 B1 IE65711 B1 IE 65711B1
- Authority
- IE
- Ireland
- Prior art keywords
- amino
- phenyl
- dione
- dioxane
- methyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 3
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 title description 2
- 108010054082 Sterol O-acyltransferase Proteins 0.000 title description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 127
- 150000001875 compounds Chemical class 0.000 claims abstract description 125
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 93
- -1 cyano, carboxyl Chemical group 0.000 claims abstract description 72
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 18
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
- 150000002367 halogens Chemical class 0.000 claims abstract description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims abstract description 3
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 3
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 3
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 202
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 60
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 59
- 125000004432 carbon atom Chemical group C* 0.000 claims description 56
- 150000001412 amines Chemical class 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- HOFQIKKOYMWXGG-UHFFFAOYSA-N 5-[(2,4-dimethoxyanilino)-[heptyl-[[4-(2-methylpropyl)phenyl]methyl]amino]methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=C1C(OC(C)(C)OC1=O)=O)N(CCCCCCC)CC1=CC=C(CC(C)C)C=C1 HOFQIKKOYMWXGG-UHFFFAOYSA-N 0.000 claims 1
- XLWLCDZDWRIGPG-UHFFFAOYSA-N 5-[(2,4-dimethoxyanilino)-[heptyl-[[4-(3-methylbutyl)phenyl]methyl]amino]methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical compound C=1C=C(OC)C=C(OC)C=1NC(=C1C(OC(C)(C)OC1=O)=O)N(CCCCCCC)CC1=CC=C(CCC(C)C)C=C1 XLWLCDZDWRIGPG-UHFFFAOYSA-N 0.000 claims 1
- DXXACIQPJKXOBY-UHFFFAOYSA-N 5-[[(4-tert-butylphenyl)methyl-heptylamino]-(2,4,6-trimethoxyanilino)methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical compound COC=1C=C(OC)C=C(OC)C=1NC(=C1C(OC(C)(C)OC1=O)=O)N(CCCCCCC)CC1=CC=C(C(C)(C)C)C=C1 DXXACIQPJKXOBY-UHFFFAOYSA-N 0.000 claims 1
- ZDMAALWJLSMMQR-UHFFFAOYSA-N 5-[[heptyl-[(4-pentylphenyl)methyl]amino]-[4-(trifluoromethyl)anilino]methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical compound C=1C=C(C(F)(F)F)C=CC=1NC(=C1C(OC(C)(C)OC1=O)=O)N(CCCCCCC)CC1=CC=C(CCCCC)C=C1 ZDMAALWJLSMMQR-UHFFFAOYSA-N 0.000 claims 1
- OVJFLKSEDFQCLM-UHFFFAOYSA-N 5-[[heptyl-[[4-(3-methylbutoxy)phenyl]methyl]amino]-(3,4,5-trimethoxyanilino)methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical compound C=1C(OC)=C(OC)C(OC)=CC=1NC(=C1C(OC(C)(C)OC1=O)=O)N(CCCCCCC)CC1=CC=C(OCCC(C)C)C=C1 OVJFLKSEDFQCLM-UHFFFAOYSA-N 0.000 claims 1
- NKFLOEVEUAQMBC-UHFFFAOYSA-N 5-[[heptyl-[[4-(3-methylbutoxy)phenyl]methyl]amino]-(3-phenylmethoxyanilino)methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione Chemical compound C=1C=CC(OCC=2C=CC=CC=2)=CC=1NC(=C1C(OC(C)(C)OC1=O)=O)N(CCCCCCC)CC1=CC=C(OCCC(C)C)C=C1 NKFLOEVEUAQMBC-UHFFFAOYSA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 4
- 230000003078 antioxidant effect Effects 0.000 abstract description 3
- 239000007787 solid Substances 0.000 description 93
- 238000000921 elemental analysis Methods 0.000 description 67
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
- 239000000243 solution Substances 0.000 description 46
- 239000002904 solvent Substances 0.000 description 44
- 239000011541 reaction mixture Substances 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 20
- 238000010992 reflux Methods 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000000746 purification Methods 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 16
- 238000012512 characterization method Methods 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 229910000372 mercury(II) sulfate Inorganic materials 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- DOBUSJIVSSJEDA-UHFFFAOYSA-L 1,3-dioxa-2$l^{6}-thia-4-mercuracyclobutane 2,2-dioxide Chemical compound [Hg+2].[O-]S([O-])(=O)=O DOBUSJIVSSJEDA-UHFFFAOYSA-L 0.000 description 9
- 235000012000 cholesterol Nutrition 0.000 description 9
- 229940074994 mercuric sulfate Drugs 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000007832 Na2SO4 Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 101150041968 CDC13 gene Proteins 0.000 description 4
- 239000004380 Cholic acid Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
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- 238000006243 chemical reaction Methods 0.000 description 4
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- 238000005886 esterification reaction Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- WJYIASZWHGOTOU-UHFFFAOYSA-N Heptylamine Chemical compound CCCCCCCN WJYIASZWHGOTOU-UHFFFAOYSA-N 0.000 description 3
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- 239000007858 starting material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- VSRBKQFNFZQRBM-UHFFFAOYSA-N tuaminoheptane Chemical compound CCCCCC(C)N VSRBKQFNFZQRBM-UHFFFAOYSA-N 0.000 description 3
- SJWOFBVBNFLWLP-UHFFFAOYSA-N 1-(1-phenylcyclopentyl)methylamine Chemical compound C=1C=CC=CC=1C1(CN)CCCC1 SJWOFBVBNFLWLP-UHFFFAOYSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000004903 negative regulation of intestinal cholesterol absorption Effects 0.000 description 2
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
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- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
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- 150000005846 sugar alcohols Polymers 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/08—1,3-Dioxanes; Hydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Peptides Or Proteins (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US56838490A | 1990-08-16 | 1990-08-16 | |
| US07/719,873 US5179216A (en) | 1990-08-16 | 1991-06-24 | N,n', n'-trisubstituted-5-bisaminomethylene-1,3-dioxane-4,6-dione inhibitors of acyl-coa:cholesterol-acyl transferase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE912900A1 IE912900A1 (en) | 1992-02-26 |
| IE65711B1 true IE65711B1 (en) | 1995-11-15 |
Family
ID=27074770
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE290091A IE65711B1 (en) | 1990-08-16 | 1991-08-15 | N,N'-di- or N,N'N'-tri-substituted-5- bisaminomethylene-1, 3-dioxane-4,6- dione inhibitors of acyl-CoA: cholesterol-acyl transferase |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5179216A (de) |
| EP (1) | EP0471493B1 (de) |
| JP (1) | JPH04244078A (de) |
| KR (1) | KR920004373A (de) |
| AT (1) | ATE138373T1 (de) |
| AU (1) | AU639129B2 (de) |
| CA (1) | CA2048891A1 (de) |
| CZ (1) | CZ280881B6 (de) |
| DE (1) | DE69119665T2 (de) |
| DK (1) | DK0471493T3 (de) |
| ES (1) | ES2088469T3 (de) |
| FI (1) | FI913894A (de) |
| GB (1) | GB2247019B (de) |
| GR (1) | GR3020776T3 (de) |
| HU (2) | HUT58717A (de) |
| IE (1) | IE65711B1 (de) |
| IL (1) | IL99065A (de) |
| MX (1) | MX9203265A (de) |
| NZ (1) | NZ239413A (de) |
| PT (1) | PT98675A (de) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX9204939A (es) * | 1991-09-06 | 1993-03-01 | American Home Prod | Inhibidores 5-bis-aminometilen-1,3-dioxan-4,6-diona n,n',n'-trisubstituidas, de la acil coenzima a: colesterol-aciltransferasa. |
| US5391768A (en) * | 1993-03-25 | 1995-02-21 | United States Surgical Corporation | Purification of 1,4-dioxan-2-one by crystallization |
| FR2781222A1 (fr) * | 1998-07-17 | 2000-01-21 | Lipha | Composes cycliques utilisables dans le traitement de dyslipidemies, de l'atherosclerose et du diabete, compositions pharmaceutiques les contenant et procede de preparation |
| US6632836B1 (en) | 1998-10-30 | 2003-10-14 | Merck & Co., Inc. | Carbocyclic potassium channel inhibitors |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1147760A (en) * | 1965-06-17 | 1969-04-10 | Sterling Drug Inc | Heterocyclic nitrogen compounds |
| US4387106A (en) * | 1982-01-26 | 1983-06-07 | American Cyanamid Company | Method of treating atherosclerosis with di(aralkyl)ureas and di(aralkyl)thioureas |
| US4387105A (en) * | 1982-01-26 | 1983-06-07 | American Cyanamid Company | Methods of treating atherosclerosis with dialkylureas and dialkylthioureas |
-
1991
- 1991-06-24 US US07/719,873 patent/US5179216A/en not_active Expired - Lifetime
- 1991-08-02 IL IL9906591A patent/IL99065A/en not_active IP Right Cessation
- 1991-08-06 AT AT91307196T patent/ATE138373T1/de not_active IP Right Cessation
- 1991-08-06 ES ES91307196T patent/ES2088469T3/es not_active Expired - Lifetime
- 1991-08-06 GB GB9116965A patent/GB2247019B/en not_active Expired - Fee Related
- 1991-08-06 JP JP3196550A patent/JPH04244078A/ja active Pending
- 1991-08-06 DK DK91307196.5T patent/DK0471493T3/da active
- 1991-08-06 EP EP91307196A patent/EP0471493B1/de not_active Expired - Lifetime
- 1991-08-06 DE DE69119665T patent/DE69119665T2/de not_active Expired - Fee Related
- 1991-08-09 CA CA002048891A patent/CA2048891A1/en not_active Abandoned
- 1991-08-14 PT PT98675A patent/PT98675A/pt not_active Application Discontinuation
- 1991-08-14 AU AU82430/91A patent/AU639129B2/en not_active Ceased
- 1991-08-14 KR KR1019910014000A patent/KR920004373A/ko active IP Right Grant
- 1991-08-15 HU HU912716A patent/HUT58717A/hu unknown
- 1991-08-15 IE IE290091A patent/IE65711B1/en not_active IP Right Cessation
- 1991-08-15 NZ NZ239413A patent/NZ239413A/xx unknown
- 1991-08-16 FI FI913894A patent/FI913894A/fi not_active Application Discontinuation
- 1991-08-16 CZ CS912552A patent/CZ280881B6/cs unknown
-
1992
- 1992-06-24 MX MX9203265A patent/MX9203265A/es unknown
-
1995
- 1995-06-20 HU HU95P/P00290P patent/HU211555A9/hu unknown
-
1996
- 1996-08-12 GR GR960402145T patent/GR3020776T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HU211555A9 (en) | 1995-12-28 |
| MX9203265A (es) | 1992-07-01 |
| HUT58717A (en) | 1992-03-30 |
| FI913894A (fi) | 1992-02-17 |
| FI913894A0 (fi) | 1991-08-16 |
| DK0471493T3 (da) | 1996-06-24 |
| GR3020776T3 (en) | 1996-11-30 |
| IL99065A (en) | 1996-01-31 |
| GB2247019A (en) | 1992-02-19 |
| GB2247019B (en) | 1994-04-13 |
| EP0471493B1 (de) | 1996-05-22 |
| CZ280881B6 (cs) | 1996-04-17 |
| ES2088469T3 (es) | 1996-08-16 |
| DE69119665D1 (de) | 1996-06-27 |
| KR920004373A (ko) | 1992-03-27 |
| CA2048891A1 (en) | 1992-02-17 |
| DE69119665T2 (de) | 1997-01-02 |
| AU8243091A (en) | 1992-02-20 |
| US5179216A (en) | 1993-01-12 |
| AU639129B2 (en) | 1993-07-15 |
| IE912900A1 (en) | 1992-02-26 |
| JPH04244078A (ja) | 1992-09-01 |
| NZ239413A (en) | 1993-03-26 |
| PT98675A (pt) | 1992-07-31 |
| HU912716D0 (en) | 1992-01-28 |
| CS255291A3 (en) | 1992-03-18 |
| ATE138373T1 (de) | 1996-06-15 |
| IL99065A0 (en) | 1992-07-15 |
| EP0471493A1 (de) | 1992-02-19 |
| GB9116965D0 (en) | 1991-09-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |